Bacteria and plants frequently use two-components signal transduction systems(TCSs) to adapt to environmental changes and to survive under stress conditions. Typical TCSs couple a transmembrane histidine protein kinase (HK), which detects changes in the environmnent, to a cytosolic response regulator (RR), which often alters gene expression. Most RRs contain two distinct domains: an N-terminal … expand

Bacteria and plants frequently use two-components signal transduction systems(TCSs) to adapt to environmental changes and to survive under stress conditions. Typical TCSs couple a transmembrane histidine protein kinase (HK), which detects changes in the environmnent, to a cytosolic response regulator (RR), which often alters gene expression. Most RRs contain two distinct domains: an N-terminal receiver domain and a C-terminal effector domain. The former autophosphorylates on a histidine residue on detecting an external stimulus. The phosphate is then transferred to an invariant aspartate residue in a highly conserved receiver domain of the response regulator. Phosphorylation activates a variable effector domain of the response regulator, which triggers the cellular response. The C-terminal effector domain contains DNA and RNA polymerase binding sites. Several dimers or monomers bind head to tail to small tandem repeats upstream of the genes. The RNA polymerase binding sites interact with the alpha or sigma subunit of RNA polymerase. The OmpR/PhoB subfamily is the largest subfamily of RRs. Members of the OmpR/PhoB subfamily include such diverse transcriptional regulators as Escherichia coli PhoB (of the phosphate assimilation pathway), Enterococcus faecium VanR (which controls resistance to the antibiotic vancomycin), and Agrobacterium tumefaciens VirG (involved in the establishment of crown gall tumors in plant. The C-terminal effector domain of the OmpR/PhoB subfamily RRs binds DNA. This DNA-binding domain is also found in proteins other than response regulators, such as Vibrio cholerea ToxR, a transmembrane protein involved in cholera toxin expression [ PUBMED:9016718 PUBMED:18052041 PUBMED:18789936 PUBMED:21634789 PUBMED:24990372 PUBMED:11934608 PUBMED:9199401 ].

The OmpR/PhoB-type DNA-binding domain has the typical fold of the wingedhelix-turn-helix DNA-binding domain. The structure of the OmpR/PhoB-type DNA-binding domain consists of three α-helices packed against two antiparallelβ-sheets, an N-terminal four-stranded antiparallel β-sheet and a C-terminal hairpin. The hairpin interacts with a short stretchof β-strand, that connects helices α1 and α2, to generate a three-stranded antiparallel β-sheet. The topology for the domain is β1-β2-β3-β4-α1-β5-α2-α3-β6-β7. The hydrophobic core ofthe domain is formed by sidechains contributed by each of the seven β-strands and three α-helices [ PUBMED:9016718 PUBMED:18052041 PUBMED:18789936 PUBMED:21634789 PUBMED:24990372 ].